Isolation of TAO1, a Protein Kinase That Activates MEKs in Stress-activated Protein Kinase Cascades

Abstract

Several components of the budding yeast pheromoneresponse pathway are conserved in mammalian mitogen-activated protein (MAP) kinase pathways. Thus, we used degenerate oligonucleotides derived from the sequence of the Saccharomyces cerevisiae protein kinase Ste20p to amplify related sequences from the rat. One of these sequences was used to clone a rat Ste20p homolog, which we called TAO1 for its one thousand and one amino acids. Northern analysis shows TAO1 is highly expressed in brain, as is a homolog TAO2. Recombinant TAO1 was expressed and purified from Sf9 cells. In vitro, it activated MAP/extracellular signal-regulated protein kinase (ERK) kinases ( 1-3). The parallel nature of the yeast and mammalian pathways was first realized when sequences of mammalian ERKs and yeast MAP kinases, KSS1 and FUS3, became available (4 -6). Subsequently, information from the yeast pathways has been exploited to identify components and understand relationships in the mammalian cascades. More than a dozen mammalian MAP kinases that lie in several distinct cascades (7,8) are now known. Fidelity in these pathways is maintained in part by the substrate specificity of the MEK family member. These cascades are differentially responsive to cellular stimuli, including proliferative and survival factors and stress. Several of the mammalian cascades share some regulatory features with yeast systems. The best delineated yeast MAP kinase pathway, activated by mating pheromones, is controlled by a receptor-G protein system and requires at least three protein kinases, Ste20p, Ste11p, and

PAK5 Kinase Is an Inhibitor of MARK/Par-1, Which Leads to Stable Microtubules and Dynamic Actin

“…For example, MARK isoforms are involved not only in regulating microtubule dynamics and the Par cell polarity determinants but also in Wnt signaling (Sun et al, 2001), and the upstream kinase MARKK/TAO-1 activates the p38 stress pathway by phosphorylating MEK3 and MEK6 (Hutchison et al, 1998). On the other hand, PAK5 is not only involved in remodelling the actin cytoskeleton, but also in inducing the JNK stress pathway Pandey et al, 2002) and in the apoptotic pathway (Cotteret et al, 2003).…”

“…We were therefore interested in the regulation of MARK. One pathway is the phosphorylation of the catalytic domain by the recently identified upstream kinase MARKK, a member of the Ste20-like kinases (Timm et al, 2003; also known as TAO-1 in the context of JNK signaling, Hutchison et al, 1998). On the other hand, MARK is an unusually large kinase, it contains several domains and could therefore interact with other potential regulatory partners.…”

MAP3Ks as central regulators of cell fate during development

“…6; Hutchison et al, 1998;Chen et al, 2003;Raman et al, 2007). The cell cycle protein, Ataxia telangiectasia mutated (ATM), is activated in response to DNA damage, and directly phosphorylates TAOk.…”

“…To date, three of these MAP3Ks have been characterized: TAOk1, TAOk2, and TAOk3. TAOk1 interacts with and activates MKK3 leading to activation of p38 (Hutchison et al, 1998). TAOk2 negatively regulates TAK1 activation of the NF B pathway after osmotic stress (Huangfu et al, 2006).…”

Comparative studies of a new subfamily of human Ste20-like kinases: homodimerization, subcellular localization, and selective activation of MKK3 and p38

“…Previously, we identified a Ste20-like kinase, KFC (kinase from chicken) (Yustein et al, 2000), from chicken embryo fibroblasts, which is related to rat thousand and one (TAO1) and TAO2 kinases (Hutchison et al, 1998;Chen et al, 1999). Together, they form a new subfamily of GCK family kinases.…”